I propose to develop a highly efficient system for expression of proteins in the keratinocytes of skin. Such system will have two important uses. One is to tolerize the host against a particular antigen. We have recently shown that restricting antigen expression to the keratinocytes in vivo decreases the immune response to subsequent exposure to the same antigen. Improving the expression system should allow extension of this concept to allergy and autoimmunity. The second is that such a system could be used for gene therapy of skin disorders.